The term “UCP” designates the family of “uncoupling proteins”; which are implicated in the uncoupling between the reoxidation of coenzymes and the phosphorylation of ADP in ATP at the level of mitochondria (Nicholls et al., Physiol. Rev., 64: 1-64, 1984).
To date, three proteins of this family have been identified: UCP-1, UCP-2 and UCP-3. UCP-1 was the first protein identified (Flax et al., FEBS Lett, 113: 299-303, 1980). It is an uncoupling protein present in brown adipose tissue (Cassard et al., Newspaper of Cell biochemistry, 43, 1990). This form of brown adipose tissue is well-known in small mammals, hibernating animals, and newborn mammals; it is a thermogenic organ which makes it possible to resist the cold by producing heat. The strong thermogenic activity of brown adipocytes comes from the presence of UCP-1. This protein dissipates part of the energy in the form of heat by an uncoupling between cellular respiration and ATP synthesis. Indeed, UCP-1 is a proton transporter present in the inner membrane of mitochondria. When the protein is activated, it catalyzes proton gradient dissipation through the membrane and short-circuits ATP synthase. Respiration, no longer coupled with ADP phosphorylation, becomes a purely thermogenic process. The uncoupling of respiration stimulates fat oxidation and generates heat.
In addition to UCP-1, two other uncoupling proteins, which are very close to UCP-1, have been identified: UCP-2 (Fleury et al., Nature Genetics, 15: 269, 1997), which one finds in a wide variety of tissues, such as the intestines, adipose tissues, muscles, the brain, and cells of the immune system; and UCP-3 (Boss O. et al., FEBS Lett, 1997), primarily located in skeletal muscles and brown adipose tissue.
These uncoupling proteins, especially UCP-2 and UCP-3, are proteins that are not well-known. However, studies have shown that they probably play a significant role in energy homeostasis (Klingenberg, J Bioenerg. Biomembr. 25: 447, 1993), noteably, in energy metabolism in general and in the control of the metabolic efficacy of food in particular.
The study of these proteins, and their encoding genes, involved in energy metabolism, have provided a new approach as well as new therapeutic targets making it possible to intervene in the regulation of energy metabolism in mammals. In particular, research has been undertaken in the development of drugs which would act, by gene therapy, on the absence or excess of UCP proteins. Up to today, on a therapeutical level, UCP proteins have only been considered potential targets in the domain of genetics, in order to treat dysfunctions or diseases related to obesity, diabetes, and hyperlipidemia, among others.
Thus, on a therapeutic level, only the use of active ingredients capable of acting on protein expression have been considered. Thus, patents JP2003113104 and JP2003113106 describe, for example, compositions made from plant extracts that are able to stimulate UCP protein expression in brown tissue adipocytes. UCP proteins have never been used, themselves, as an active ingredient.